The studies proposed in this research application will apply in vivo31P nuclear magnetic resonance spectroscopy (31P MRS) to the study of brain dysfunction and neuronal death in patients with Alzheimer's disease (AD). The overall goals are to develop a non-invasive diagnostic test for AD, and to validate data from 31P MRS as a biologic measure of dementia severity that can be used to monitor the clinical course of AD. Patients with AD and control subjects will be recruited from the Memory Disorders Unit (MDU) of the Massachusetts Alzheimer's Disease Research Center and undergo an identical series of neurological and neuropsychological examinations as well as a 31P MRS study. All participants will also undergo 1H MR brain imaging with computerized morphometric analysis. Correlations among clinical, 31P MRS and 1H MR morphometric studies will test the hypothesis that distinctive functional impairments in AD precede structural changes and are superior as indices of neuronal degeneration and disease progression. We hypothesize that the high energy phosphates decrease significantly early in the course of AD and that the 31P MR spectra may contribute to the early diagnosis of AD by revealing increases in phosphodiesters that are characteristic markers of neuronal membrane degeneration in AD. We expect that phosphorus metabolite abnormalities will occur in the early stages of dementia before gross anatomic changes, based upon morphometric assessment of 1H MR brain images, can be observed. We will relate the extent of abnormalities in 31P MRS spectroscopy and 1H MR morphology to clinical estimates of different states of disease severity. This project is multidisciplinary and involves investigators with special skills in clinical neurology and neuroimaging. The project builds upon existing Clinical Core, Neuropathology Core and Administrative Core units in the Massachusetts ADRC. The proposed research will provide basic information regarding brain energy metabolism, neuronal membrane composition and brain morphology in cognitive intact elderly subjects, and will determine whether distinctive changes in these measures occur in AD.